小鼠生后发育过程中轮廓乳头味蕾形态及其α-味蛋白表达

应用组织学与免疫荧光组织化学手段从不同侧面系统研究了小鼠生后早期发育过程中轮廓乳头味蕾数量、形态及α-味蛋白表达的变化规律;结果表明:出生当天小鼠轮廓乳头内尚未有味蕾存在,但在生后早期迅速发育,在出生后最初4周内味蕾的数量、大小迅速显著地增长(P<0.001),味蕾的形态也从幼年期的椭圆形到成年期的长椭圆形,味蕾细胞明显延长;发育过程中离体味蕾的形态大小同组织学研究结果具有一致性;α-味蛋白阳性味蕾与阳性细胞在出生后最初2周内显著增长(P<0.001)。结果表明,味蕾发育过程是一个结构与功能相适应的过程。     

哺乳动物味觉的细胞生物学

味觉对于生命具有重要作用,在一定程度上决定了动物对食物的选择。哺乳动物味觉识别主要依赖于舌味蕾中的味细胞,味蕾由50～100个极化的神经上皮细胞聚集而成。通过对味蕾细胞的分析显示,味蕾是一种精巧的单元结构。这篇文章综述了味蕾细胞的形态、结构功能、细胞生物学活性以及味觉信息的传导。     

哺乳动物味蕾细胞分型及其细胞间信息传递

味觉是动物基本的生理感觉之一,在人类的感官研究方面,味觉一直滞后于视觉、嗅觉、触觉和听觉.味蕾是味觉的主要感受器,由于传统的细胞生物学研究手段很难在味觉研究中得到应用,人类和动物味觉的信号传递与编码机制目前还处于探索阶段,是目前的研究热点之一.近年来,随着现代分子细胞生物学和微电子传感器技术的发展和应用,味觉研究取得了较大进展.本文主要对近年来对味蕾结构和味细胞间的信号传递研究成果进行了综述,重点介绍了味细胞分型及其特征、味蕾细胞间信号传递途径及其编码机制.     

漫谈味觉

漫谈味觉陈英水（福建省松溪县第一中学３５３５００）味蕾是味觉感受器,分布在舌乳头、舌穴等处．舌乳头是舌面上许多粘膜小突起。它有４种类型,丝状、菌状、叶状和轮廓乳头。舌穴是舌乳头旁边的细管。味蕾的分布有年龄差异。成人味蕾主要分布于舌面（特别是舌尖和舌侧...     

黄颡鱼口须味蕾分布模式及味蛋白α-味导素的表达

为探讨黄颡鱼口须味蕾的分布模式及其α味导素的表达,应用连续石蜡切片和环境扫描电镜对口须味蕾的数量、形态和分布进行了研究,并用整体包埋免疫荧光组化方法检测了黄颡鱼4种口须味蕾中α味导素的表达。结果显示:黄颡鱼口须味蕾主要分布在口须中间2/3区域,存在三种类型的味蕾:Ⅰ型与Ⅱ型味蕾突起于上皮表面,Ⅲ型味蕾平齐于周围上皮;味蕾细胞中有α味导素的强表达。结果提示,黄颡鱼口须味蕾的数量、形态及其分布模式是其适应底栖生活习性的结果;α味导素在各种口须味蕾中的强烈表达说明α味导素在黄颡鱼味觉感知与信息传导过程中有重要意义,也意味着脊椎动物味觉信号转导存在着共同路径     

味觉受体第一家族与味觉识别

哺乳动物味觉受体第一家族(taste receptor family 1 member,T1R)的发现提供了甜味与鲜味(氨基酸味)味觉识别与味觉概念一个重要的新视野。T1R包括T1R1、T1R2、T1R3三个成员。这些受体属于G蛋白偶联受体家族第3亚型,其中T1R2 T1R3以异二聚体形式共表达并参与甜味识别,而T1R1 T1R3也以异二聚体形式共表达并参与鲜味(氨基酸味)识别。对T1R的系列研究证明了味细胞对甜味和鲜味(氨基酸味)的选择性识别及其外周味觉编码的逻辑性。     

味觉神经损伤与再生对动物味觉功能影响的研究进展

味觉的感受器是味蕾,来源于味蕾的味觉信号通过味觉神经传递到味觉中枢神经系统。鼓索神经和舌咽神经是支配舌面味蕾的两大主要味觉神经,它们分别支配着前舌和后舌的味蕾。味觉神经损伤可以引起所支配的味蕾萎缩、退化、消失,进而导致部分味觉功能受损,受损的味觉功能则可以在味觉神经再生后得到恢复。味觉神经交叉再生支配大鼠模型是研究中枢神经系统可塑性变化的重要平台。味觉神经交叉再生支配后,动物的行为学反应和味觉神经的电生理特性都发生了很大的变化。本文综述味觉神经损伤、再生以及味觉神经交叉支配对动物味觉功能的影响,并对味觉神经交叉再生支配动物模型以后的研究方向进行展望。味觉神经损伤、再生和交叉再生支配的研究不仅有助于揭示味觉神经系统可塑性变化的机制,也将为临床上寻找治疗味觉障碍患者的方法和技术提供理论基础和新的思路。     

α-味导素及其在苦味转导中的作用

α-味导素(α-gustducin)是一种转导素(transducin)样味觉特异性G蛋白,它在多种脊椎动物的味细胞中都有表达,为脊椎动物味觉感受所必需。在哺乳动物的II型味细胞中,约有30%￣40%表达α-味导素,并且在其微绒毛处的表达水平最高。行为学、电生理学以及分子生物学的研究显示,α-味导素是苦味转导的重要调控因子,它在苦味的信号转导中发挥着极其重要的作用。     

味觉结构是如何产生的

在五种感觉当中,人们对味觉的了解最少。味蕾是将从食物及其他来源获得的化学刺激传输到神经细胞的感觉器官,而神经细胞又将这些信息传送至大脑的味觉中心。位于舌头表面和两侧的小突起里的味蕾被称为味觉乳头。     

大鼠舌乳头酶组织化学及扫描电镜的研究

实验采用酶组织化学法和扫描电镜对大鼠舌乳头的酶活性及其表面结构进行了观测。结果表明。大、鼠舌菌状乳头和轮廓乳头的味蕾处Mg^2 -ATPase为强阳性反应（ ）,ChEase为中等阳性反应（ ）,使用ChE Ag^ 染色方法显示。味蕾含有丰富的神经末梢,结果提示ATP可能是味觉传导中神经递质或调质。     

Development of anterior gustatory epithelia in the palate and tongue requires epidermal growth factor receptor.

We characterized the gustatory phenotypes of neonatal mice having null mutations for epidermal growth factor receptor (egfr(-/-)), brain-derived neurotrophic factor (bdnf(-/-)), or both. We counted the number and diameter of fungiform taste buds, the prevalence of poorly differentiated or missing taste cells, and the incidence of ectopic filiform-like spines, each as a function of postnatal age and anterior/posterior location. Egfr(-/-) mice and bdnf(-/-) mice had similar reductions in the total number of taste buds on the anterior portions of the tongue and palate. Nonetheless, there were significant differences in their gustatory phenotypes. EGFR deficiency selectively impaired the development of anterior gustatory epithelia in the mouth. Only bdnf(-/-) mice had numerous taste buds missing from the foliate, vallate, and posterior fungiform papillae. Only egfr(-/-) fungiform taste papillae had robust gustatory innervation, markedly reduced cytokeratin 8 expression in taste cells, and a high incidence of a filiform-like spine. Egfr/bdnf double-null mutant mice had a higher frequency of failed fungiform taste bud differentiation. In bdnf(-/-) mice taste cell development failed because of sparse gustatory innervation. In contrast, in young egfr(-/-) mice the abundance of axons innervating fungiform papillae and the normal numbers of geniculate ganglion neurons implicate gustatory epithelial defects rather than neural defects.     

Developmental time course of peripheral cross‐modal sensory interaction of the trigeminal and gustatory systems

Few sensory modalities appear to engage in cross‐modal interactions within the peripheral nervous system, making the integrated relationship between the peripheral gustatory and trigeminal systems an ideal model for investigating cross‐sensory support. The present study examined taste system anatomy following unilateral transection of the trigeminal lingual nerve (LX) while leaving the gustatory chorda tympani intact. At 10, 25, or 65 days of age, rats underwent LX with outcomes assessed following various survival times. Fungiform papillae were classified by morphological feature using surface analysis. Taste bud volumes were calculated from histological sections of the anterior tongue. Differences in papillae morphology were evident by 2 days post‐transection of P10 rats and by 8 days post in P25 rats. When transected at P65, animals never exhibited statistically significant morphological changes. After LX at P10, fewer taste buds were present on the transected side following 16 and 24 days survival time and remaining taste buds were smaller than on the intact side. In P25 and P65 animals, taste bud volumes were reduced on the denervated side by 8 and 16 days postsurgery, respectively. By 50 days post‐transection, taste buds of P10 animals had not recovered in size; however, all observed changes in papillae morphology and taste buds subsided in P25 and P65 rats. Results indicate that LX impacts taste receptor cells and alters epithelial morphology of fungiform papillae, particularly during early development. These findings highlight dual roles for the lingual nerve in the maintenance of both gustatory and non‐gustatory tissues on the anterior tongue. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 626–641, 2016     

NT4/5 mutant mice have deficiency in gustatory papillae and taste bud formation.

Neurotrophins are key determinants for controlling the survival of peripheral neurons during development. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4/5) exert their action through a common trkB receptor but independently support gustatory sensory neurons. To assess the role of NT4/5 during development, we examined the postnatal development and maintenance of fungiform taste buds in mice carrying a deletion of NT4/5. The absence of NT4/5 results in embryonic deficits in gustatory innervation and a reduced number of fungiform papillae at birth. No degenerative deficits of fungiform papillae were observed for the first 3 weeks of postnatal development. However, these remaining fungiform papillae were smaller in appearance and many did not contain taste pores. By postnatal day 60, there was 63% decrease in the number of fungiform papillae, and remaining papillae were smaller in size or modified into filiform-like spines. These papillae had either no taste bud or a taste bud with a reduced number of taste cells compared to controls. These findings demonstrate that the NT4/5 gene functions in the maintenance of fungiform gustatory papillae and raises the possibility for an earlier role in development.     

Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) are essential for the survival of geniculate ganglion neurons, which provide the sensory afferents for taste buds of the anterior tongue and palate. To determine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BDNF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpression of BDNF or NT4 caused a 93 and 140% increase, respectively, in the number of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in the dorsal midregion and ventral tip of the tongue. No alterations were observed in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many were small, poorly innervated, and lost postnatally. To explain the loss of nerve innervation to fungiform papillae, the facial nerve of developing animals was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons in BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innervation to filiform papillae was observed. In addition, some papillae that formed in transgenic mice had two taste buds (instead of one) and were frequently arranged in clusters of two or three papillae. These results indicate that target-derived BDNF and NT4 are not only survival factors for geniculate ganglion neurons, but also have important roles in regulating the development and spatial patterning of fungiform papilla and targeting of taste neurons to these sensory structures.     

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds

The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin.     

Building sensory receptors on the tongue

Neurotrophins, neurotrophin receptors and sensory neurons are required for the development of lingual sense organs. For example, neurotrophin 3 sustains lingual somatosensory neurons. In the traditional view, sensory axons will terminate where neurotrophin expression is most pronounced. Yet, lingual somatosensory axons characteristically terminate in each filiform papilla and in each somatosensory prominence within a cluster of cells expressing the p75 neurotrophin receptor (p75NTR), rather than terminating among the adjacent cells that secrete neurotrophin 3. The p75NTR on special specialized clusters of epithelial cells may promote axonal arborization in vivo since its over-expression by fibroblasts enhances neurite outgrowth from overlying somatosensory neurons in vitro. Two classical observations have implicated gustatory neurons in the development and maintenance of mammalian taste buds—the early arrival times of embryonic innervation and the loss of taste buds after their denervation in adults. In the modern era more than a dozen experimental studies have used early denervation or neurotrophin gene mutations to evaluate mammalian gustatory organ development. Necessary for taste organ development, brain-derived neurotrophic factor sustains developing gustatory neurons. The cardinal conclusion is readily summarized: taste buds in the palate and tongue are induced by innervation. Taste buds are unstable: the death and birth of taste receptor cells relentlessly remodels synaptic connections. As receptor cells turn over, the sensory code for taste quality is probably stabilized by selective synapse formation between each type of gustatory axon and its matching taste receptor cell. We anticipate important new discoveries of molecular interactions among the epithelium, the underlying mesenchyme and gustatory innervation that build the gustatory papillae, their specialized epithelial cells, and the resulting taste buds.     

FGF signaling regulates the number of posterior taste papillae by controlling progenitor field size

The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP). Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry) genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK) signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1(-/-);Spry2(-/-) embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway.     

Taste bud density in circumvallate and fungiform papillae of the bovine tongue

Taste bud quantitation may provide useful parameters for interspecies comparisons of the gustatory system. The present study is a morphometric analysis of bovine taste papillae. Circumvallate and fungiform papillae from six bovine tongues were serially sectioned and, following staining, analyzed. Circumvallate papillae were found to have a mean volume of 3.66 +/- 2.82 mm3, a mean number of taste buds per papilla of 445 +/- 279, and a mean taste bud density of 155 +/- 112 buds/mm3. Values for lateral fungiform papillae for the same three parameters were 0.384 +/- 0.184 mm3, 13.2 +/- 13.4, and 40.8 +/- 46.6 buds/mm3, respectively. Values for dorsal fungiform papillae were 0.438 +/- 0.246 mm3, 4.39 +/- 4.78, and 14.0 +/- 17.1 buds/mm3, respectively. Circumvallate papillae were found to have a significantly greater volume, number of taste buds per papilla, and taste bud density than either type of fungiform papilla. These data should serve as background for biochemical, endocrinological, or neurological studies involving the bovine tongue.     

Expression of tryptophan hydroxylase in developing mouse taste papillae

Gustatory papillae and associated taste buds receive and process chemical information from the environment. In mammals, their development takes place during the late phase of embryogenesis. However, the cellular factors that regulate the differentiation of taste papillae remain largely unknown. Here, we show by quantitative real time RT-PCR that both isoforms of tryptophan hydroxylase (TPH1 and TPH2), the first and rate limiting enzyme of serotonin (5-HT) synthesis, are expressed in developing circumvallate papillae. Immuno-staining experiments further indicated that TPH is localized both in gustatory fibers and in differentiated taste receptor cells. These results point to the synthesis of 5-HT in gustatory papillae, and allow one to hypothesize that the development of taste buds might be modulated by serotonin.     

Lingual deficits in neurotrophin double knockout mice

Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF^?/? and wild-type mice. Taste papillae morphology was severely distorted in BDNF^?/?xNT-3^?/? mice compared to single BDNF^?/? and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF^?/? and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF^?/?xNT-3^?/? mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF^?/?xNT-3^?/? mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development.